Ethambutol Hydrochloride Tablets

» Ethambutol Hydrochloride Tablets contain not less than 95.0 percent and not more than 105.0 percent of the labeled amount of C10H24N2O2·2HCl.

Packaging and storage— Preserve in well-closed containers.

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USP Aminobutanol RS

C4H11NO 89.14

USP Ethambutol Hydrochloride RS

Identification— Triturate a quantity of finely ground Tablets, equivalent to about 100 mg of ethambutol, with 3 mL of methanol in a glass mortar. Add 5 mL of methanol to obtain a suspension, then filter through a funnel lined with a suitable filter paper (Whatman No. 42 or the equivalent) previously moistened with methanol, and collect the filtrate in a beaker containing 100 mL of acetone. Stir the mixture, and allow crystallization to proceed for 15 minutes. Decant the liquid, and gently dry the crystals with the aid of a current of air until the odor of methanol no longer is detectable: a portion of the crystals so obtained responds to the Identification tests under Ethambutol Hydrochloride.

Dissolution

711

—

Medium: water; 900 mL.

Apparatus 1: 100 rpm.

Time: 45 minutes.

Phosphate buffer— Dissolve 38.0 g of monobasic sodium phosphate and 2.0 g of anhydrous dibasic sodium phosphate in water to obtain 1000 mL of solution.

Bromocresol green solution— Dissolve 200 mg of bromocresol green in 30 mL of water and 6.5 mL of 0.1 N sodium hydroxide. Dilute with Phosphate buffer to 500 mL, mix, and add 0.1 N hydrochloric acid to adjust to a pH of 4.6 ± 0.1.

Standard preparation— Dissolve an accurately weighed quantity of USP Ethambutol Hydrochloride RS in water, and dilute quantitatively with water to obtain a solution having a known concentration of about 0.1 mg per mL.

Procedure— Into 3 separate, glass-stoppered, 50-mL centrifuge tubes pipet (a) 1 mL of a filtered portion of the solution under test, (b) 1 mL of Standard preparation, and (c) 1 mL of water to provide a blank. Add 5.0 mL of Bromocresol green solution to each tube, mix, add 10.0 mL of chloroform to each, insert the stoppers, and shake the mixtures vigorously. Allow the mixtures to separate, discard the upper aqueous layers, and filter the 3 chloroform layers through separate pledgets of cotton. Determine the amount of C10H24N2O2·2HCl dissolved from absorbances, at the wavelength of maximum absorbance at about 415 nm, obtained from the test solution in comparison with those obtained from the Standard solution, using the blank to set the instrument.

Tolerances— Not less than 75% (Q) of the labeled amount of C10H24N2O2·2HCl is dissolved in 45 minutes.

Uniformity of dosage units

905

: meet the requirements.

Limit of aminobutanol—

Borate buffer, Standard solution, and Fluorescamine solution— Prepare as directed in the test for Limit of aminobutanol under Ethambutol Hydrochloride.

Test solution— Place a number of Tablets, equivalent to 400 mg of ethambutol hydrochloride, in a beaker, cover with acetone, and allow to stand for 15 minutes. Decant the acetone, dry the tablets, and remove the coating. Grind the tablet cores in a mortar to a fine powder, moisten with methanol, and triturate to a fine paste. Transfer the mixture with the aid of methanol to a 100-mL volumetric flask, dilute with methanol to volume, and mix. Filter the mixture through a dry, folded filter paper. Pipet 25 mL of the filtrate into a 200-mL volumetric flask, and dilute with water to volume. Allow to stand for 15 minutes, and filter through a dry, folded filter paper, discarding the first cloudy portions of the filtrate. The clear filtrate is the Test solution.

Procedure— Proceed as directed for Procedure in the test for Limit of aminobutanol under Ethambutol Hydrochloride.

Assay—

Buffer— Mix 1.0 mL of triethylamine with 1 L of water, and adjust with phosphoric acid to a pH of 7.0.

Mobile phase— Prepare a filtered and degassed mixture of Buffer and acetonitrile (1:1). Make adjustments if necessary (see System Suitability under Chromatography

621

Standard preparation— Dissolve an accurately weighed quantity of USP Ethambutol Hydrochloride RS in water to obtain a solution having a known concentration of about 0.30 mg of ethambutol hydrochloride per mL.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 30 mg of ethambutol hydrochloride, to a 100-mL volumetric flask, dissolve in water with the aid of sonication, and dilute with water to volume. Filter the solution, discarding the first 10-mL portion.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 200-nm detector and a 4.6-mm × 15-cm base-deactivated column that contains 5-µm packing L10. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of ethambutol hydrochloride (C10H24N2O2·HCl) present in the portion of Tablets taken by the formula:

100C(rU / rS)

in which C is the concentration, in mg per mL, of USP Ethambutol Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Behnam Davani, Ph.D., M.B.A. Senior Scientific Liaison 1-301-816-8394	(SM12010) Monographs - Small Molecules 1
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 3124

Pharmacopeial Forum: Volume No. 28(5) Page 1406